Diabetes & Ketogenesis

Type 1 vs. Type 2 Diabetes?

Type 1 - lack insulin production & signaling

Type 2 - insulin resistance / sensitivity

How does hyperglycemia occur?

glucose binding N-terminal Val of hemoglobin beta chains → HbA1c

what happens when injecting insulin?

insulin helps recruit glucose transporter, facilitating glucose entry into cells

what happens when patient inject too much insulin?

excessively activating glucose uptake & storage → hypoglycemia (low blood glucose)

when does ketogenesis occur?

• ⬆acetyl-CoA (due to increased fat & AA catabolism)

• glucose absence (when glucagon & epinephrine signaling dominate)

  • no enough carb - no enough OAA - limiting factor

• ketone bodies can be used as alternate fuel in other tissues & brain

what are the 3 types of ketone bodies?

β-hydroxybutyrate, acetoacetate, acetone

• acetone - waste

How many ATP does each acetyl-CoA make thru TCA?

10

• NADH - 3×2.5 = 7.5

• FADH - 1×1.5 = 1.5

• GTP - 1

how does ketoacidosis occur?

• accumulation of ketone bodies

• blood buffering system initially compensate + H⁺ absorption bone bicarbonate & renal secretion

  • eventually bicarbonate depleted → acidosis

• in absence of insulin:

  • ⬇insulin - can't recruit GLUT transporter

  • fat catabolism starts → ⬆acetyl-CoA

  • but ⬇OAA → TCA can’t occur → ketogenesis